Mechanism of differentiation and growth of pancreatic βcells by newly identified growth factor, NTAK, and its application for regenerative medicine in diabetes mellitus

我们对胰腺β细胞的再生分化和细胞凋亡机制进行了研究，为糖尿病的治疗开辟了新的途径。在这项研究中，我们研究了神经和胸腺来源的ErbB激酶激活剂(NTAK)和CD9的可能参与，NTAK是新发现的EGF家族的生长因子，CD9是EGF家族信号转导的调节剂之一。我们发现成人和胎儿胰腺产生NTAK，它们分别定位于β细胞和胎儿胰腺上皮细胞，包括内分泌前体细胞。胰岛细胞也表达CD-9。这些结果表明，除了参与胰腺的发育外，NTAK和CD-9可能还参与了胰腺β细胞的分化和/或增殖机制。体外对NTAK的多肽研究表明，NTAK的部分多肽序列具有增殖活性，而另一部分多肽序列对β细胞株MIN6细胞的增殖有抑制作用，提示NTAK信号转导可能参与了阳性和阴性(细胞凋亡？)β细胞增殖和/或分化的调控途径。在胰腺β细胞中，NTAK的详细信号转导途径(S)有待进一步研究。

We have been studied on the mechanism of regeneration and differentiation, and apoptosis of pancreatic β cells to develop the new therapeutic approach to diabetes mellitus. In this research, we investigated the possible involvement of neural-and thymus-derived activator for ErbB kinases (NTAK), newly identified growth factor which belongs to the EGF family, and CD 9, one of the modulators of EGF family signal transduction. We demonstrated the adult and fetal pancreas produced NTAK which is localized in β cells and fetal pancreatic epithelial cells including endocrine precursor cells, respectively. CD-9 also expressed on islet cells. These results suggested that NTAK and CD-9 may be involved in the mechanism of differentiation and/or proliferation of pancreatic β cells in addition to the development of pancreas.In vitro peptide study of NTAK revealed that partial sequence of peptides of NTAK showed the activity of proliferation, while some other part of peptide sequence inhibited the proliferation of β cell line, MIN6 cells, suggesting that NTAK signal transduction may be involved in both positive and negative (apoptotic?) regulatory pathways for β cell proliferation and/or differentiation. Further study is necessary to elucidate the detailed signal transduction pathway(s) of NTAK in pancreatic β cells.